Metastatic melanoma has a very poor prognosis and systemic therapies - both cytotoxic and biological - have not improved outcome in this disease so far. For this reason, novel therapeutic strategies are urgently required. Angiogenesis represents a relevant process to modulate in melanoma, as pro-angiogenic ligands and their receptors are overexpressed and have been found to correlate with disease progression and prognosis. The angiogenic axis may be targeted at many different levels, which are still being defined. This article presents an overview of the importance of angiogenesis in melanoma and draws attention to some of the key molecules that are currently being targeted rationally within clinical studies. We discuss a number of anti-angiogenic and anti-vascular agents and their mechanisms of action. An overview of the efficacy and toxicity of these treatments in clinical trials performed so far in melanoma is presented and future directions for anti-angiogenic strategies in melanoma are considered.